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Genome-wide analysis of mRNA decay patternsduring early Drosophila development

机译:果蝇早期发育过程中mRNA衰减模式的全基因组分析

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摘要

Background: The modulation of mRNA levels across tissues and time is key for the establishment and operation ofthe developmental programs that transform the fertilized egg into a fully formed embryo. Although thedevelopmental mechanisms leading to differential mRNA synthesis are heavily investigated, comparatively littleattention is given to the processes of mRNA degradation and how these relate to the molecular programscontrolling development. Results: Here we combine timed collection of Drosophila embryos and unfertilized eggs with genome-wide microarray technology to determine the degradation patterns of all mRNAs present during early fruit flydevelopment. Our work studies the kinetics of mRNA decay, the contributions of maternally and zygoticallyencoded factors to mRNA degradation, and the ways in which mRNA decay profiles relate to gene function, mRNAlocalization patterns, translation rates and protein turnover. We also detect cis-regulatory sequences enriched intranscripts with common degradation patterns and propose several proteins and microRNAs as developmentalregulators of mRNA decay during early fruit fly development. Finally, we experimentally validate the effects of asubset of cis-regulatory sequences and trans-regulators in vivo. Conclusions: Our work advances the current understanding of the processes controlling mRNA degradationduring early Drosophila development, taking us one step closer to the understanding of mRNA decay processes inall animals. Our data also provide a valuable resource for further experimental and computational studiesinvestigating the process of mRNA decay.
机译:背景:跨组织和时间调节mRNA水平是建立和运行将受精卵转化为完全形成的胚胎的发育程序的关键。尽管已深入研究了导致差异mRNA合成的发展机制,但对mRNA降解的过程以及这些与控制发育的分子程序之间的关系却很少关注。结果:在这里,我们将果蝇胚胎和未受精卵的定时采集与全基因组微阵列技术相结合,以确定果蝇早期发育过程中存在的所有mRNA的降解模式。我们的工作研究了mRNA衰减的动力学,母本和经合子编码的因素对mRNA降解的贡献,以及mRNA衰减图谱与基因功能,mRNA定位模式,翻译率和蛋白质更新相关的方式。我们还检测到具有常见降解模式的富含顺式调控序列的转录本,并提出了几种蛋白质和microRNA作为早期果蝇发育过程中mRNA衰减的发育调控因子。最后,我们通过实验验证了体内顺式调节序列和反式调节剂亚集的作用。结论:我们的工作推动了对果蝇早期发育过程中控制mRNA降解的过程的当前理解,使我们对所有动物的mRNA衰变过程的理解又迈进了一步。我们的数据还为进一步研究mRNA降解过程的实验和计算研究提供了宝贵的资源。

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